Chronic hepatitis B virus (HBV) affects over 350 million worldwide and over 1.5 million Americans, placing them at risk for developing cirrhosis, liver failure, and hepatocellular carcinoma. The natural history of HBV is variable but tends to follow 4 phases: immune tolerant (IT), immune active (IA), inactive, and clearance. These phases are dependent on age of exposure and both viral and host characteristics. Current guidelines recommend treatment only in those with immune active disease. Although viral suppression is achievable in most patients with oral anti-HBV therapy, cure is not possible because of persistent virus in hepatocytes in the form of covalently closed circular DNA and the integration of HBV DNA into the human genome. The Hepatitis B Research Network (HBRN), established in 2008, is composed of 21 adult and 7 pediatric sites, a Virology/Serology Core, an Immunology Center, and a Data Coordinating Center. During the initial funding period, the Network established an Adult and Pediatric Cohort study, an Adult IA study, an Adult and Pediatric IT study, and several Ancillary studies that focus on specific aspects of various clinica scenarios. Over the initial funding cycle, the HBRN has enrolled 1869 adults and 368 children. The bio-specimen repository contains over 188,000 adult and 7300 pediatric plasma and serum samples, and over 1479 adult and 205 pediatric whole blood DNA specimens. The primary goals of the HBRN over the course of the next funding cycle are to perform clinical trials on chronic HBV in adults and children, prospectively quantify outcomes in the database cohort, and leverage these data and previously collected bio-specimens to better understand disease progression, and validate clinically meaningful biomarkers. The specific aims of these studies are as follows: 1. To successfully complete the studies which have been initiated during the initial funding period. 2. To successfully complete all Ancillary Studies already approved by the HBRN during the initial funding period. 3. To undertake new Ancillary Studies in Adults and Children based on the clinical material and samples collected during the previous funding period. During the initial funding period, several novel populations were enrolled, which will allow the HBRN to address several gaps in knowledge such as (a) characterize histologic, virologic, and immunologic features of those with indeterminate HBV (neither IA, IT, or inactive), (b) determine the clinical implications of stopping anti-viral therapy in those outside of the IT ad IA trials. (c) treatment for hepatitis delta virus, and (d) assess the long-term effects of tenofovr on bone health.